The Yodo River, usually called the Seta River in Shiga Prefecture, begins at the southern outlet of the lake in Ōtsu. There is a dam there to regulate the lake level. Further downstream, the Seta flows into Kyoto Prefecture and changes its name to the Uji River, and then merges with two other rivers, namely the Katsura River and the Kizu River in Kyoto Prefecture. The Katsura has its headwaters in the mountains of Kyoto Prefecture, while the Kizu comes from Mie Prefecture. From the three-river confluence, the river is called the Yodo River, which flows south, through Osaka, and on into Osaka Bay. In Osaka, part of the river has been diverted into an artificial channel; the old course in the heart of Osaka is called the Kyū-Yodo River (literally, 'Former Yodo River').

It serves as a source of water for irrigation and also powers hydroelectric generators.